Collaboration and Knowledge

Professor Geoff McCaughan believes in the power of curiosity. It’s what’s driven him for over 40 years.

“I still remember looking through a microscope and seeing something no one had seen before. In that moment, I realised that every discovery is a step closer to understanding, even when it raises more questions along the way. Finding those answers might take years, but it’s a necessary journey of exploring the unknown, and it’s that curiosity that really drives me,” says Geoff, Head of the McCaughan Laboratory at the Centre for Cancer Innovations.

Geoff is one of Australia’s leading hepatologists. Today, at the Centenary Institute, his research delves into chronic liver disease, exploring the complexities of liver autoimmunity and the nuances of achieving liver transplant tolerance, along with the clinical treatment of hepatitis B and C and the management of hepatocellular cancer.

Geoff’s eyes light up as he casts his mind back to a significant find in the late 1990s. “Together with Mark Gorrell and PhD student Miriam Levey, we discovered for the first time that a molecule called fibroblast activation protein (FAP) was highly expressed in human inflammatory fibrotic liver disease, which predisposes you to liver cancer. I knew in that moment that the discovery would drive our research for many years.” 

Human inflammatory fibrotic liver disease, or liver fibrosis, is a buildup of scar tissue on the liver. Geoff’s discovery, along with key collaborators including fellow Centenary Institute researcher, Professor Mark Gorrell, helped establish FAP as a marker for disease progression and tissue scarring in cirrhosis.

Their scientific leadership and innovation has played a key role in defining FAP’s place in liver disease biology, with hope that it could soon lead to new treatments that stop scarring to prevent cancer from developing, as well as for treating cancers.

Collaboration is something that Geoff regards as critical in basic and clinical research, as well as a legacy to be passed to future generations of scientists.

Connecting the dots

“Understanding disease and how each piece fits into the bigger picture helps guide the clinical decisions we make. Those decisions are connected to the discoveries, but also stand on their own, helping patients in ways we might not have expected. Finding those answers might take years, and it might not be me who finds them, but it’s about starting and being part of the journey.” 

Collaborations include those with immunologists, Associate Professor Patrick Bertolino and Associate Professor David Bowen, to better understand liver transplant tolerance. Together, they are investigating how the liver interacts with the immune system to reduce rejection risk, with the goal of better outcomes and fewer medication side effects for patients.

This passion for connecting the dots is evident in his various roles, working in both clinical medicine and laboratory-based research at Sydney’s Royal Prince Alfred Hospital (RPAH) and the Centenary Institute.

Geoff articulates the connections between basic and clinical research with an example of a case involving a child in need of a liver transplant due to a genetic disease. By connecting the case to a Centenary researcher, Professor Mat Francios, they facilitated research that allowed the use of a drug to halt the progression of the disease, postponing the need for a liver transplant.

“A couple of years ago, I was at an RPAH meeting and the paediatricians presented a boy with a genetic disease who needed a liver transplant. I’m interested in molecules, so I was curious to know what the molecule was. When they told me, I was immediately excited – I knew that work was being done on that specific molecule at Centenary.

“The patient’s paediatric team and Mat Francios’s team were able to be connected, and using specific tissues from the child, a drug was able to be tested on those tissues, and long story short, it hasn’t cured his disease, but it stopped its progression and the need for a transplant.”

It’s an example of the interconnected nature of basic and clinical research and how curiosity-driven questions can lead to important advancements. It’s also a real-life demonstration of the impact of the Centenary Institute’s unique geographical location, between the neighbouring USYD and RPA Hospital. This position optimises the “bed-to-bench-to-bed” research cycle. 

Currently, projects on primary liver cancer are revealing mechanisms of disease that had not been previously contemplated. “Working with basic scientists such as Dr Jinbiao Chen, Associate Professor Mainthan Palendira,
Dr Felix Marsh-Wakefield and Dr Angela Ferguson, together with PhD students, is inspiring and exciting,” says Geoff. “Their youth drives innovation and deep understanding of disease that hopefully in the future will lead to new approaches for patients.

“My journey in clinical medicine and research has been incredibly fulfilling. It used to be the norm to see patients suffer and die from chronic liver disease, but now liver transplantation offers a lifeline and significantly improves lives. I’m driven by the discoveries that change lives, whether it’s understanding how a new molecule works or questioning findings.” 

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